Engagement of the B-cell antigen receptor (BCR) initiated by the Src kinase Lyn triggers rapid signaling cascades, leading to proliferation, differentiation or growth arrest of B cells. The Janus kinase (JAK)-STAT (signal transducer and activator of transcription) pathway, activated through cytokine receptors, mediates similar responses. Hypothesizing that Src and JAK pathways engage in crosstalk in B-cell signaling, we studied wild-type and Lyn-null B-cell lines, which express BCR. We found that activated BCR results in tyrosine phosphorylation of JAK-STAT, which required Lyn. To confirm that STAT activation is not due to JAK, we cloned the chicken homologs of JAK1 and JAK2 and made their antisense constructs. In cells expressing antisense JAK1 and JAK2, tyrosine phosphorylation of STAT was not inhibited following BCR stimulation. Using activation loop-specific phosphotyrosine antibodies, we did not detect phospho-JAK1 and phospho-JAK2 after BCR stimulation. The JAK inhibitor AG490 did not inhibit the tyrosine phosphorylation of Lyn or STAT after BCR simulation. An in vitro phosphorylation assay showed that Lyn directly phosphorylates STAT3. In an electrophoretic mobility shift assay, BCR stimulation led to enhanced DNA binding of the STAT3 in DT40, but not in the Lynnull cells. We conclude that BCR engagement activates the STAT pathway via Lyn, independent of JAK.
Purpose: To establish a quantitative complexity measure for IMRT plans. Methods: We propose a quantitative complexity index (CI) of IMRT plans that considers the dose variations within each IMRT field and compares to dose variations uniform rectangular fields of comparable size. The ratio of area to perimeter of a 1‐D dose profile is a measure of complexity, as the complexity of dose profile increases, this ratio would decrease as the perimeter would increase for a given area. This ratio would be greatest for an open field. By normalizing ratio of an IMRT field to that of uniform field of similar size, the variation of this ratio with field size would be eliminated. The complexity index of a plan would be weighted average of complexity indices of its individual fields. A graph of gamma versus CI would guide the clinical physicist in accepting an IMRT QA in a more rational manner. The calculated dose distributions were used to calculate the CI. We exposed EDR films in solid phantom to uniform and intensity modulated fields using 6 MV photons. The films were normal to CAX of beams. Results: The gamma analyses of these films were performed using 3% dose, 3mm DTA criteria with a 10% dose threshold. Some of the uniform and the modulated fields were measured and analyzed repeatedly to evaluate the random uncertainty. We noticed a gradual decrease in the percent of pixels with gamma values ≤1 with increasing complexity — from about 94% for large uniform fields to about 83% for modulated fields. The decrease was significant compared to the random uncertainty. Small open fields (4×4) had lower % pixel with gamma ≤1 than larger fields (10×10) (88%). Conclusion: A quantitative complexity analysis was established and would be a useful tool in evaluating gamma analyses of IMRT QA.
Purpose: The plastic scintillation detector (PSD) is a promising dosimeter for in vivo dosimetry due to its high spatial resolution and excellent water equivalency. The arbitrary orientation of PSD, when placed inside a patient body, may affect its relative response. This study investigates the directional dependence of the response of PSD in photon beams by Monte Carlo simulations. Method and Materials: Two PSDs (BC‐400 and BCF‐12), each coupled to an optical fiber stem, are modeled. The directional dependences of the response of both PSDs in a water phantom are studied for a 6 MV spectral photon beam and a 300 keV mono‐energetic photon beam. Different optical fiber core materials (plastic, glass, and air) are used in the calculation model to study the influence of the optical fiber materials upon the directional dependence of the detector response. Results: For the majority of angles between the detector axis and the incident beam direction, the response of the PSDs is within 1∼2 % irrespective of the photon energy or the optical fiber material used. For the case when the optical fiber stem is pointing to the source, the PSDs with glass or air cored optical fibers show larger deviations (6 % for 6 MV beam and 15 % for 300 keV beam) while the response for the PSDs with plastic cored optical fibers is still within 2 %. Conclusion: If plastic is used for the fiber core, the directional dependence is not of concern at 2 % level in photon beams. If glass or air is used for the fiber core, the PSD response has a 6 % deviation or more when the optical fiber stem is pointing to the source, which is probable for in vivo applications as the orientation of the detector cannot be guaranteed. Supported by the NCI (1R01CA120198‐01A2)
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